a. Field of Invention
This invention relates to the process for the production of substituted 2-oxocyclohexaneacetic acid esters and the intermediates used for their production. The substituted 2-oxocyclohexaneacetic acid esters produced by the present process are themselves intermediates for the manufacture of useful analgesic and anti-inflammatory compounds described in Mobilio et al, U.S. Pat. No. 4,616,028, Oct. 7, 1986, which is herein incorporated by reference.
More specifically, this invention relates to the production of 1,4-disubstituted 2-oxocyclohexaneacetic acid esters of formula (V) ##STR1## wherein R and R.sup.1 are lower alkyl; R.sup.2, R.sup.3, and R.sup.5 are hydrogen, or lower alkyl wherein lower alkyl contains 1 to 6 carbon atoms; each R.sup.4 is independently selected from the group consisting of hydrogen, or lower alkyl wherein lower alkyl contains 1 to 6 carbon atoms, or R.sup.3 is joined to the R.sup.4 which is cis to the carbon bearing R.sup.3 to form --CH.sub.2 --.sub.m wherein m is 2 to 3, or R.sup.5 is joined to the R.sup.4 which is cis to R.sup.5 to form --CH.dbd.CH--CH.dbd.CH--.
b. Prior Art
The closest prior art to the present invention is:
Mobilio et al, U.S. Pat. No. 4,616,028, Mobilio et al disclose the 1,4-disubstituted 2-oxocyclohexaneacetic acid esters of formula (V) and the process for producing analgesic and anti-inflammatory compounds from said 2-oxocyclohexaneacetic acid esters of formula (V). Mobilio et al employ the expensive phenylselenenyl chloride in the production process of the 2-oxocyclohexaneacetic acid esters of formula (V). The present invention provides a novel process for producing said 2-oxocyclohexaneacetic acid esters in high yield, from inexpensive reagents which can be conveniently carried out on a large scale without the necessity for purifying intermediate compounds by chromatography. The present process also provides a high yield of the preferred isomer of 2-oxocyclohexaneacetic acid esters of formula (V).
A. Asselin et al. J. Med. Chem., 19, 787 (1976) disclose an alternate production method for a substituted 2-oxocyclohexaneacetic acid esters of formula (V).
A. Asselin et al, U.S. Pat. No. 4,057,559, Nov. 8, 1977, disclose still another process for the production of a substituted 2-oxocyclohexaneacetic acid esters of formula (V).